Systems and Methods for On Line Finishing of Cellular Blood Products Like Platelets Harvested for Therapeutic Purposes

ABSTRACT

Blood processing systems and methods establish on line communication between a container and a source of blood containing leukocytes and platelets, such as a human donor. The systems and methods create a centrifugal field between the source of blood and the container that separates from the blood an unfinished suspension of platelets having a first physiologic characteristic different than the desired physiologic characteristic. The systems and methods pump the unfinished platelet suspension outside the centrifugal field through a finishing device. The finishing device changes the first physiologic characteristic to the desired physiological characteristic, thereby creating the finished platelet suspension. The systems and methods convey the finished platelet suspension from the finishing device directly into the container. The systems and methods function without interrupting the on line communication between the container and the source of blood.

RELATED APPLICATION

This application is a continuation of co-pending U.S. patent applicationSer. No. 10/024,733 filed 19 Dec. 2001, which is a division of U.S.patent application Ser. No. 09/548,190 filed 13 Apr. 2000, which is adivision of U.S. patent application Ser. No. 09/223,212 filed 30 Dec.1998, which is a division of U.S. patent application Ser. No. 08/606,189filed 23 Feb. 1996.

FIELD OF THE INVENTION

The invention generally relates to blood processing systems and methods.In a more specific sense, the invention relates to systems and methodsfor removing leukocytes from blood components collected for therapeuticpurposes.

BACKGROUND OF THE INVENTION

Today blood collection facilities routinely separate whole blood intoits various therapeutic components, such as red blood cells, platelets,and plasma.

One separation technique that is in widespread use today uses a multipleblood bag system. The bag system includes a primary blood bag and one ormore transfer bags, which are integrally connected to the primary bag bytubing. The technique collects from a donor a single unit (about 450 ml)of whole blood in the primary blood bag. The donor is then free toleave.

The donor's whole blood later undergoes centrifugal separation withinthe primary bag into red blood cells and plasma rich in platelets. Theplasma rich in platelets is expressed out of the primary bag into atransfer bag, leaving the red blood cells behind. The plasma rich inplatelets then undergoes further centrifugal separation within thetransfer bag into a concentration of platelets and plasma poor inplatelets. The plasma poor in platelets is expressed from the transferbag into another transfer bag, leaving the concentration of plateletsbehind.

Using multiple blood bag systems, all three major components of wholeblood can be collected for therapeutic use. However, the yield for eachcomponent collected is limited to the volume of the components that arecontained in a single unit of whole blood. Furthermore, because redblood cells are retained, United States governmental regulationsprohibit collecting another unit of whole blood from the donor until sixweeks later.

Certain therapies transfuse large volumes of a single blood component.For example, some patients undergoing chemotherapy require thetransfusion of large numbers of platelets on a routine basis. Multipleblood bag systems simply are not an efficient way to collect these largenumbers of platelets from individual donors.

On line blood separation systems are today used to collect large numbersof platelets to meet this demand. On line systems perform the separationsteps necessary to separate concentration of platelets from whole bloodin a sequential process with the donor present. On line systemsestablish a flow of whole blood from the donor, separate out the desiredplatelets from the flow, and return the remaining red blood cells andplasma to the donor, all in a sequential flow loop.

Large volumes of whole blood (for example, 2.0 liters) can be processedusing an on line system. Due to the large processing volumes, largeyields of concentrated platelets (for example, 4×10¹¹ plateletssuspended in 200 ml of fluid) can be collected. Moreover, since thedonors red blood cells are returned, the donor can donate whole bloodfor on line processing much more frequently than donors for processingin multiple blood bag systems.

Regardless of the separation technique used, when collecting bloodcomponents for transfusion, it is desirable to minimize the presence ofimpurities or other materials that may cause undesired side effects inthe recipient. For example, because of possible febrile reactions, it isgenerally considered desirable to transfuse red blood cells andplatelets that are substantially free of leukocytes, particularly forrecipients who undergo frequent transfusions.

Several United States patents are directed to the removal of leukocytesfrom red blood cells and platelet components in multiple blood bagsystems. For example, see U.S. Pat. Nos. 4,767,541; 5,089,146;5,100,564; and 5,128,048.

U.S. Pat. No. 5,427,695 is directed to the removal of leukocytes fromplatelet-rich plasma during on line blood processing.

The platelet-rich suspension product obtained using prior on line bloodcollection systems and methods may still lack the desired physiologiccharacteristics imposed by the end user (typically a blood bank orhospital) for long term storage and transfusion. For example, theplatelet-rich suspension may include residual leukocytes that, whilevery small in relation to the leukocyte population in whole blood, arestill greater than the leukocyte population standards desired by the enduser.

Therefore, despite significant advances in blood processing technology,a need still exists for further improved systems and methods forremoving undesired matter like leukocytes from blood components in a waythat lends itself to use in high volume, on line blood collectionenvironments.

SUMMARY OF THE INVENTION

The invention provides on line blood processing systems and methods forobtaining a finished platelet suspension having a desired physiologiccharacteristic. In a preferred embodiment, the desired physiologiccharacteristic comprises a desired reduced residual population ofleukocytes.

The systems and methods that embody features of the invention establishon line communication between a container and a source of bloodcontaining leukocytes and platelets, such as a human donor. The systemsand methods create a centrifugal field between the source of blood andthe container. The centrifugal field separates from the blood anunfinished suspension of platelets having a first physiologiccharacteristic different than the desired physiologic characteristic. Ina preferred embodiment, the unfinished platelet suspension contains aninitial leukocyte population greater than the desired residual leukocytepopulation.

According to the invention, the systems and methods pump the unfinishedplatelet suspension outside the centrifugal field through a finishingdevice. The finishing device changes the first physiologiccharacteristic to the desired physiological characteristic, therebycreating the finished platelet suspension. In a preferred embodiment,the finishing device reduces the leukocyte population by filtration. Thesystems and methods convey the finished platelet suspension from thefinishing device directly into the container for storage or transfusion.

The systems and methods that embody the features of the inventionfunction without interrupting the on line communication between thecontainer and the source of blood.

Other features and advantages of the invention can be found in thedrawings, accompanying description, and claims of this Specification.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatic view of a blood processing system, whichincludes a finishing device that embodies the features of the invention;and

FIG. 2 is a diagrammatic view of a centrifugal blood processing systemthat can be use in association with the finishing device shown in FIG.1.

The invention may be embodied in several forms without departing fromits spirit or essential characteristics. The scope of the invention isdefined in the appended claims, rather than in the specific descriptionpreceding them. All embodiments that fall within the meaning and rangeof equivalency of the claims are therefore intended to be embraced bythe claims.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

FIG. 1 shows in diagrammatic form an on line blood processing system 10that embodies features of the invention. According to the invention, theon line system 10 provides a finished, high quality platelet-rich bloodproduct (PLT_(FIN)), with a significantly reduced residual population ofleukocytes and/or other enhanced physiological properties, suited forlong term storage and transfusion.

As used in this Specification, the term “on line blood separationprocess” refers to a blood separation system or method that (i)establishes communication between a blood source (typically, a humanblood donor) and an extracorporeal flow path; (ii) draws a blood volumefrom the donor into the flow path; and (iii) maintains communicationwith the circulatory system of the donor for at least a portion of thetime that the blood volume undergoes separation within theextracorporeal flow path.

As used in this Specification, an “on line blood separation process” canseparate the blood volume either in a continuous manner or in aninterrupted manner. However, an “on line blood separation process”maintains communication between the flow path and the donor for at leasta portion of the time the separation process occurs within the flowpath, regardless of specific timing or sequencing of the separationprocess itself.

As used in this Specification, an “on line blood separation process” caninclude external or internal valves or clamps to interrupt flow withinthe path to or from the donor. However, in the context of thisSpecification, such valves or claims do not break the communicationbetween the blood donor and the flow path. Instead, the valves or clampscontrol fluid flow within the path while maintaining communicationbetween it and the blood donor.

The on line system 10 draws whole blood (WB) from a donor through aphlebotomized tubing flow path 12. WB contains, as its principalcomponents, red blood cells, platelets, leukocytes, and plasma. Thesystem 10 adds anticoagulant to the drawn WB and conveys anticoagulatedWB into a centrifugal field 14 for processing.

In the centrifugal field 14, the system 10 ultimately separatesanticoagulated WB into two components. The first component is a redblood cell concentration. It is desirable that the red blood cellconcentration also carry with it a majority of the leukocyte population(LK) present in the WB. For this reason, the first component is referredto as RBC_(LK+).

RBC_(LK+) is returned to the donor during processing. This avoidsdepletion of the donor's red blood cell and leukocyte populations whilehigh volume yields of platelets are obtained.

The second component comprises an unfinished platelet-rich plasmasuspension PLT_(UN). PLT_(UN) is considered “unfinished” because theplatelet-rich plasma suspension still lacks the desired physiologiccharacteristics imposed by the end user (typically a blood bank orhospital) for long term storage and transfusion. Centrifugal processingwithin the field 14 often cannot provide these desired characteristics.

The specific physical makeup of the platelet-rich suspension comprisingPLT_(UN) can vary. The makeup will largely depend upon the efficiency ofthe centrifugal separation process in terms of the how many plateletsare separated (i.e., the platelet yields) and how much platelet-poorplasma product is withdrawn and not returned to the donor.

As used in this Specification, PLT_(UN) is intended to encompass anysuspension in which platelets are present in concentrations greater thanin whole blood. PLT_(UN) can comprise what is commonly referred to asplatelet-rich plasma (PRP) or platelet concentrate (PC), or suspensionsof platelets and plasma lying in between.

PLT_(UN) can include, in addition to platelets, other components oringredients, depending upon the choice of the end user. For example,PLT_(UN) can include essentially only plasma as the platelet suspensionmedia. Alternatively or in addition to plasma, PLT_(UN) can include aspecially formulated platelet storage media to suspend the platelets.

The structural details of the centrifugation field 14 can vary and arenot essential to the invention. For example, the field 14 can comprise acentrifuge and multiple stage centrifugal processing chambers of thetype shown in Brown U.S. Pat. No. 5,427,695 or Brown U.S. Pat. No.5,370,802, both of which are incorporated herein by reference.

As FIG. 2 shows in diagrammatic form, the multiple stage processingchambers that Brown '695 and '802 embody separate WB into RBC and PRP ina first stage separation chamber 16. The special fluid flow dynamicsthat occur in the first stage chamber 16 shown in Brown '802 or '695keep a large majority of leukocytes out of PRP and with the RBC in thefirst stage chamber 16 for return to the donor as RBC_(LK+). The specialfluid flow dynamics occurring in the first stage chamber 16 in Brown'802 or Brown '695 also provide a high yield of platelets in the PRP.

In Brown '802 or '695, PRP is transported from the first stage chamber16. A portion is recirculated back to the WB entering the first stagechamber 16, and the rest is conveyed into a second stage chamber 18. ThePRP is separated in the second stage chamber 18 into PC andplatelet-poor plasma (PPP).

PC retained in the second stage chamber 18 is later resuspended in avolume of PPP or (optionally) a suitable platelet storage medium fortransfer from the second stage chamber as PLT_(UN). A portion of the PPPis returned to the donor, while another portion of PPP is retained foruse as a recirculation or keep-open or rinse-back or resuspension media,or for storage for fractionation or transfusion.

One reason why PLT_(UN) can be considered “unfinished” in the context ofthe above described system is the presence of residual leukocytes in theplatelet suspension. This residual population of leukocytes with theplatelets, while small, still can be greater than the leukocytepopulation standards demanded by the end user.

Often, centrifugal processing alone often is not effective at isolatingenough leukocytes from PRP to meet these demands. Unintendedperturbations and secondary flows along the interface between RBC andplasma, where leukocytes reside, can sweep lighter leukocyte speciesaway from RBC into the plasma. Other desirable flow patterns that sweepheavier leukocytes species in the interface back into the RBC mass canalso fail to develop to their fullest potential. The dynamic processesunder which leukocytes are separated from platelets duringcentrifugation are complex and subject to variation from donor to donor.

Additional steps can be provided to augment the primary centrifugalseparation process to thereby reduce the number of residual leukocytespresent in PLT_(UN). For example, as disclosed in Brown '695, aleukocyte filter 20 can be provided after the first stage chamber 16 tofilter leukocytes from PRP before entering the second stage chamber 18for separation into PC and PPP. The filter 20 is preferably locatedoutside the centrifugal field 14, being connected by a rotatingumbilicus arrangement 22 of conventional construction. Alternatively,though, the filter 20 can be located within the centrifugal field 14.

Alternatively, or in combination with such other ancillaryleukocyte-reduction devices, PLT_(UN) can be subject to particle bedseparation effects within the centrifugal field 14 to separateleukocytes from the platelets. Still, the degree of leukocyte reductiondemanded by the user can exceed the capabilities of even these ancillarysteps during the centrifugal separation process.

For this reason (see FIG. 1), the system 10 includes an in linefinishing device 24 located outside the centrifugal field 14. A pump 26conveys PLT_(UN) under pressure from the centrifugal field 14 throughthe finishing device 24. In FIG. 1, the pump 26 is shown downstream ofthe centrifugal field 14. Alternatively, the pump 26 could be locatedupstream of the centrifugal field 14, thereby supplying the requisitemachine pressure to convey PLT_(UN) from the centrifugal field 14.

The finishing device 24 serves to affect a desired alteration in themakeup or physiological of PLT_(UN) that could not be effectivelyachieved in the centrifugal field 14, such as, for example, a furtherincremental reduction in the leukocyte population. The in line finishingdevice 24 performs its function on line, while the donor remainsconnected in communication with the system 10.

The output of the finishing device 24 is a finished platelet-richsuspension (PLT_(FIN)). PLT_(FIN) is considered “finished” because theplatelet-rich plasma suspension possesses the desired physiologiccharacteristics imposed by the end user for long term storage andtransfusion. In the context of the illustrated embodiment, theplatelet-rich suspension comprising PLT_(FIN), possesses a more-reducedleukocyte population and/or additional physiological attributes notpresent in PLT_(INI).

As used in this Specification, the term “reduced” or “more-reduced” doesnot denote that all the residual leukocytes have been removed. The termis intended to more broadly indicate only that the number of residualleukocytes have been incrementally reduced by the finishing device 24,compared with the number before processing by the finishing device.

Other physiological attributes that the finishing device can provideinclude (INSERT . . . . )

The finishing device 24 can accomplish its function by centrifugation,absorption, columns, chemical, electrical, and electromagnetic means. Inthe illustrated and preferred embodiment, the finishing device 24comprises a filter that employs a non-woven, fibrous filter media 28.

The composition of the filter media 28 can vary. The media 28 comprisesfibers that contain nonionic hydrophillic groups and nitrogen-containingbasic functional groups. Fibers of this type are disclosed in Nishimuraet al U.S. Pat. No. 4,936,998, which is incorporated herein byreference. Filter media containing these fibers are commercially sold byAsahi Medical Company. Filter media containing these fibers havedemonstrated the capacity to remove leukocytes while holding down theloss of platelets. Alternatively, the filter media 28 can comprisefibers that have been surface treated as disclosed in Gsell et al. U.S.Pat. No. 5,258,127 to increase their ability to pass platelets whileremoving leukocytes. Gsell et al. U.S. Pat. No. 5,258,127 is alsoincorporated herein by reference.

Furthermore, because the pump 26 is used to convey PLT_(INI) through thefinishing device 24, the external machine pressure it creates can beused to overcome passive resistance of the finishing media 28.Therefore, the finishing media 28 can be densely packed within thefinishing device 24 to achieve maximum efficiencies.

The system 10 conveys PLT_(FIN) to one or more containers 30 suitablefor transfusion or long term storage. The container(s) 30 intended tostore PLT_(FIN) can be made of polyolefin material (as disclosed inGajewski et al U.S. Pat. No. 4,140,162) or a polyvinyl chloride materialplasticized with tri-2-ethylhexyl trimellitate (TEHTM). These materials,when compared to DEHP-plasticized polyvinyl chloride materials, havegreater gas permeability that is beneficial for platelet storage.

The system 10 shown in FIG. 1 can be readily incorporated into acontinuous single or double needle on line blood processing systems.

As used in this Specification, the “on line blood separation process”differs from a multiple blood bag process. In a multiple blood bagprocess, the donor's circulatory system does not remain in communicationwith the flow path where separation of the collected blood volumeoccurs. In a multiple blood bag system, after a given blood volume iscollected in the primary bag, the donor's circulatory system isdisconnected from the primary bag before separation occurs within thebag. Also, in a multiple blood bag system, the separation processes donot occur continuously. The first stage separation of red blood cellsand plasma rich in platelets and the second stage separation ofplatelets from plasma occur at different points in time as separate,discontiguous steps.

Various features of the inventions are set forth in the followingclaims.

1. (canceled)
 2. An on line blood processing method for obtaining afinished concentrated blood cell suspension having a reduced residualleukocyte population (1) establishing on line communication between acontainer and a source of blood having a first population of leukocytes,(2) creating, while maintaining the on line communication between thecontainer and the source, a centrifugal field between the source and thecontainer that separates from the blood a first concentrated blood cellsuspension and a second concentrated blood cell suspension having aninitial population of leukocytes less than the first population ofleukocytes and greater than the reduced residual population ofleukocytes, (3) pumping, while maintaining the on line communicationbetween the container and the source, substantially all of the secondconcentrated blood cell suspension outside the centrifugal field througha finishing device outside the centrifugal field, the finishing deviceoperating to reduce the initial leukocyte population in the secondconcentrated blood cell suspension, thereby creating a finishedconcentrated blood cell suspension having a reduced residual leukocytepopulation less than the initial population of leukocytes and suited forlong term storage and transfusion without further processing, and (4)conveying, while maintaining the on line communication between thecontainer and the source, substantially all of the finished concentratedblood cell suspension from the finishing device directly into thecontainer and not a separation device.
 3. A method according to claim 2wherein the finishing device comprises a filter media.
 4. A methodaccording to claim 2 further including providing a pump outside of thecentrifugal field for pumping substantially all of the secondconcentrated blood cell suspension from the centrifugal field throughthe finishing device, and wherein the pumping is carried out by saidpump.